Cell culture has developed from the growth of single cell bacteria, yeast and molds which are encased with a tough cell wall to growth of mammalian cells. Mammalian cell culture is much more complex because the cells are more delicate and have a more complex nutrient requirement. Large scale culture of bacterial type cells is well developed and the culture techniques less demanding than mammalian cells. The bacterial cells are grown in large volumes of liquid medium and can be vigorously agitated without any significant damage. Mammalian cells on the other hand cannot withstand excessive turbulent action without damage to the cells and must be provided with a complex nutrient medium to support growth.
In addition, mammalian cells have other special requirements such that most animal cells must attach themselves to some surface to duplicate. On a small scale mammalian cells have been grown in containers with small wells to provide anchors for the cells. The cell culture in the containers with microwells do not provide surface area to grow mammalian cells on a large scale basis. Microcarrier beads were developed which provide surface area for the cultured cells to attach. It can also be placed in a vessel which contains a large volume of culture medium.
A bio-reactor containing microcarrier beads with attached cells must be agitated to provide a uniform suspension in a fresh supply of nutrient. The bio-reactor chambers have internal propellers or agitation devices which are motored driven. The culture vessels contain moving parts within the vessel to cause agitation for the suspension of the mammalian cells on the carrier beads. In addition to propellers, a culture vessel with rotating flexible sheets of nylon have been used. "The Large-Scale Cultivation of Mammalian Cells", Scientific American, January 1983, Volume 28, No. 1. pp. 36-43.
The bio-reactors with the internal moving parts cause shearing stress on the cells. The beads collide with each other and damage the cells. The collision of the beads during agitation of the medium in the bio-reactor prevents the usage of high density of microcarriers in the present bio-reactors. One system uses a satellite filter in a separate vessel from the bio-reactor. This is necessary because the microcarrier beads cannot be recycled through the filtering apparatus because the beads are too large to go through the filter pores.
The bio-reactor used to culture mammalian cells utilize mechanical parts which stress the cells. Large numbers of cells cannot be grown due to the impact on the cells.